The present invention is related to the prolonged delivery of an active agent. More particularly, it is directed to an improved method of making a banded active agent dosage form which is useful for delivering a beneficial agent to a fluid environment of use.
Tablets, capsules, caplets and many other types of devices have been used for dispensing a beneficial agent to a fluid environment of use. Easy manufacture of a device that provides for prolonged delivery of an active agent in a controlled and predictable manner continues to be a goal, especially in the area of drug delivery.
U.S. Pat. No. 4,290,426 to Luschen et al describes a cylindrical dispenser for releasing a beneficial agent into a fluid environment at a rate that is governed by the fluid-induced relaxation of a polymeric agent contained within the dispenser. The cylindrical dispenser includes an impermeable container that has within it a reservoir and a passageway from the reservoir to the exterior of the container. The reservoir contains a polymer and a beneficial agent. The polymer imbibes fluid from the environment and thereby undergoes relaxation, releasing the beneficial agent from the device. The amount of agent released is dependent on the rate of relaxation of the polymer over time.
Coated dosage forms have also been suggested for delivery of a controlled amount of a beneficial agent over a prolonged period of time. U.S. Pat. No. 5,256,440 describes a process for producing a film coated dosage form. A continuous groove is inscribed in a dosage form core. A latex film is coated onto the core, the groove defining a fixed zone and a detachable zone for the film. The detachable portion of the latex film detaches when it is exposed to the environment of use, thereby exposing a discrete portion of the dosage form core surface. The remainder of the film remains attached to the dosage form core. The exposed portion of the dosage form surface erodes and releases active agent to the environment of use.
Coated tablets for constant and prolonged drug release are described by Conte et al in J. Controlled Release, Vol. 26, (1993) pages 39-47. These GEOMATRIX(trademark) Systems are swellable matrices that are coated or tabletted with polymeric barrier layers. Release performances of the systems are modulated as a result of the restriction of the releasing surface by the polymeric barrier layer coatings. As the extent of coating of the system""s surface is increased, the release kinetics of the system shift toward constant release. These systems are further described in U.S. Pat. No. 4,839,177 to Colombo et al.
U.S. Pat. No. 5,534,263 describes a banded dosage form which is useful for the sustained delivery of an active agent formulation to a fluid environment of use. The active agent dosage form is a matrix that has on its surface two or more insoluble bands. The dosage form described provides significant advantages over other prior art devices for the sustained delivery of an active agent.
It has been observed that banded devices such as those described in U.S. Pat. No. 5,534,263 (""263 patent), which is incorporated herein by reference in its entirety, have significant advantages for prolonged delivery of an active agent formulation to a fluid environment of use. It has now been discovered that if the active agent formulation matrix is provided with at least one groove, prior to the banding process described in the ""263 patent, the groove can be used as a register to orient the dosage form during the banding process. Additionally, the groove allows for more uniform deposition of the banding material. In that manner, improved dosage forms are provided and savings and manufacturing advantages are achieved.
Accordingly, the present invention is directed to an improved method and system for manufacturing banded dispensing devices, to improved articles of manufacture, and to components that facilitate manufacture of the devices.
In one aspect, the invention comprises an active agent dosage form for the prolonged delivery of an active agent formulation to a fluid environment of use, the dosage form comprising an active agent formulation matrix having at least one groove circumscribing a portion of the surface thereof and an insoluble band positioned in the groove.
In another aspect the invention comprises a blank for formation of an active agent dosage form for controlled delivery of an active agent, the blank comprising an active agent formulation matrix having at least one groove circumscribing a portion of the surface thereof.
In a further aspect the invention comprises a banding system for fabricating an active agent dosage form comprising means for orienting a blank having a groove and means for forming a band in the groove.
The invention comprises the following characteristics and features, either alone or in combination with one or more of each other:
An active agent dosage form for the prolonged delivery of an active agent formulation to a fluid environment of use, the dosage form comprising an active agent formulation matrix having at least one groove circumscribing a portion of the surface thereof and an insoluble band located in the groove; the dosage form wherein the groove has the shape of a notch; the dosage form wherein the groove has a continuous concave shape; the dosage form wherein the depth of the groove is between 0.1 and 3 mm; the dosage form wherein the width of the groove is between 0.5 and 10 mm; the dosage form wherein the outer surface and bands are coated to form a smooth, exterior surface; and the dosage form having more than one groove circumscribing a portion of the surface thereof and an insoluble band located in each groove.
A blank for formation of a pharmaceutical dosage form for controlled delivery of an active agent, the blank comprising an active agent formulation matrix having at least one groove circumscribing a portion of the surface thereof; the blank wherein the groove has the shape of a notch; the blank wherein the groove has a continuous concave shape; the blank wherein the depth of the groove is between 0.1 and 3 mm; the blank wherein the width of the groove is between 0.5 and 10 mm; the blank wherein the groove functions as a location register; the blank wherein the groove is adapted to cooperate with a printing means; the blank wherein the groove is adapted to cooperate with a printing means having a latex source; and the blank wherein the groove is adapted to cooperate with a printing means having a latex source selected from acrylate esters.
A system for fabricating the dosage form from a blank comprising an active agent formulation matrix and at least one groove on the surface thereof, the system comprising means for orienting the blank by means of a groove in the blank, and means for forming a band in a groove; the system including means for transporting the blank; the system wherein the means for orienting the blank includes means registering with one or more of the grooves on the blank; the system wherein the means for orienting the blank includes a rotatable wheel; the system wherein the band forming material comprises a latex of acrylate polymers; the system wherein the acrylate polymers comprise copolymers of ethylacrylate and methylmethacrylate; and the system wherein the means for forming a band in a groove comprises printing means.
A method of preparing an active agent dosage form for the prolonged delivery of an active agent formulation to a fluid environment of use, the dosage form comprising an active agent formulation matrix having at least one groove circumscribing a portion of the surface thereof and a band of insoluble material positioned in the groove, the method comprising forming a blank having a groove corresponding to a desired location of the insoluble band, and coating the groove with the insoluble material.